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. Author manuscript; available in PMC: 2017 Jul 12.
Published in final edited form as: Chemistry. 2015 Dec 10;22(11):3856–3864. doi: 10.1002/chem.201503986

Scheme 2.

Scheme 2

Synthesis of dyad inhibitors, varying alkyl length and alkyne. A) H2SO4, acetone (96%); B) p-TsCl, DMAP, DCM/pyridine (89 %); C) N-Boc-alkylamine, K2CO3, THF (2: 78%, 3: 91%, 4: 96%); D) TFA, H2O (quant.); E) Ac-l-Ala-OH, EDC, HOBt, DMF (towards 8: 54%, 9: 37%, 10: 74%); F) i. chloroacetic anhydride, DCM; ii. NaN3, DMF (toward 11: quant., toward 12: 94%, toward 13: quant.); G) alkyne, CuSO4, sodium ascorbate, tBuOH/H2O (quant. by LC-MS). DMAP= 4-(dimethylamino)pyridine, TFA=trifluoroacetic acid, EDC = 3-(ethyliminomethylidenamino)-N,N-dimethyl-propan-1-amine, HOBt= hydroxybenzotriazole, DCM=dichloromethane; DMF= dimethylformamide.